Serum Lipid Concentrations in Subjects With Phenylketonuria and Their Families Terry J. DeClue, MD; Jim Davis, MD; Dawn M. Schocken, MPH; Ruth Kangas, RD; Steve A. Benford \s=b\ To determine if subjects with phenylketonuria receiving diets significantly lower in cholesterol and saturated fat had serum lipid concentrations different from those of their family members, we measured serum concentrations of to- tal cholesterol, high-density lipoprotein cholesterol, and total triglycerides in the probands with phenylketonuria, their parents, and their siblings. Eleven adults (seven women and four men) and 16 children (eight girls and eight boys) were studied. Ten subjects (four girls and six boys) had phenylketonuria. Subjects with phenylketonuria consumed less cholesterol (0.02 vs 0.41 mmol/d ) and fat (median, 21% vs 39.5% of total calories), and their diets had a higher ra- tio of polyunsaturated to saturated fatty acids (median, 2.0 vs 0.2) than did their siblings without phenylketonuria. The diet of the parents was similar to that of their offspring without phenylketonuria. No differences were noted be- tween the subjects with phenylketonuria (consuming a diet lower in saturated fat and cholesterol) and their siblings without phenylketonuria in serum concentrations of total cholesterol (median, 3.34 vs 3.07 mmol/L); high-density li- poprotein cholesterol (median, 1.44 vs 1.37 mmol/L); low\x=req-\ density lipoprotein cholesterol (median, 1.44 vs 1.09 mmol/ L); or triglycerides (median, 0.89 vs 0.54 mmol/L). We conclude that previously reported lipoprotein abnormali- ties noted between unrelated subjects with and without phenylketonuria may not be due to differences in dietary intake, but rather due to a (genetic) predisposition of the population with phenylketonuria toward lower serum lipid concentrations. (AJDC. 1991;145:1266-1268) Phenylketonuria (PKU) is an inborn error of metabo¬ lism secondary to a deficiency of phenylalanine hy- droxylase. It is inherited as an autosomal recessive trait, and dietary intervention is the only treatment currently available. The basis of the PKU diet is to restrict pheny¬ lalanine intake early in life. To supply the recommended daily allowances of protein, carbohydrates, and fats, spe¬ cial casein hydrolysate formulas are used. As the patient ages, various low-protein solid food exchanges are added to the diet. Because of the reduction of animal protein in the patients' diet, they generally consume a lower per¬ centage of calories from fat and cholesterol than does the general population.1-2 It has been suggested that the PKU diet is responsible for the lower values of total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high- density lipoprotein cholesterol (HDL-C) noted in the subject with PKU.13 We evaluated lipoproteins in children with PKU and their families to determine if other (famil¬ ial) factors might be responsible for these changes in se¬ rum total cholesterol. SUBJECTS AND METHODS Seven families with at least one child attending the PKU clinic at the University of South Florida were enrolled. Ten children (four girls and six boys) with PKU (median age, 7.3 years; range, 0.75 to 30 years) and six siblings without PKU (two girls and four boys; median age, 7.1 years; range, 5 to 17 years) were evaluated. Two subjects with PKU were older than 25 years (27 and 30 years) and had not been prescribed a phenylalanine-restricted diet at birth. At the time of the study, all subjects with PKU were receiving an appropriate phenylalanine-restricted diet. Eleven parents (seven women and four men) with a median age of 33 years (range, 24 to 48 years) were also studied. All subjects were euthyroid and none was obese. The study was reviewed and approved by the Institutional Review Board of the University of South Florida; informed consent was obtained from each family member before enrollment. Each subject studied completed a 3-day food diary before blood collection. The food diary was an¬ alyzed by a registered dietitian using Nutritionist III (N-Squared Computing, Silverton, Ore) for content of protein; carbohydrate; fat; cholesterol; and monounsaturated, polyunsaturated, and saturated fatty acids. The dietary information for each individ¬ ual was averaged and reported as median and range for a 24-hour period. On the day of blood collection, following an overnight fast, the subjects' heights and weights were measured and they were al¬ lowed to sit for 10 to 15 minutes before blood samples were col- lectied through an antecubital vein. Following collection, the se¬ rum was separated immediately. Serum concentrations of total cholesterol, HDL-C, triglycérides, and thyrotropin were mea¬ sured in all subjects, and phenylalanine levels were determined in the probands with PKU. The serum sample for HDL-C was refrigerated at 4°C until assayed 48 to 72 hours after collection. Serum samples for analysis of total cholesterol, triglycérides, and thyrotropin were frozen at — 70°C until assay. Total cholesterol, HDL-C, and triglycéride levels were measured at the University of Miami using nationally standardized methods previously de- Accepted for publication June 17, 1991. From the Department of Pediatrics, University of South Florida Health Sciences Center. Presented in part at the Southern Society for Pediatric Research Meeting, January 19, 1990; New Orleans, La. Reprint requests to University of South Florida, MDC Box 45, 12901 Bruce B. Downs Blvd, Tampa, FL 33612-4799 (Dr DeClue).